Topoisomerases are important biochemical targets for chemotherapeutic intervention in a number of different cancers. These enzymes are important in many central genetic events of both normal and transformed cells. This proposal is based upon new findings that establish a link between type II topoisomerase and the physical ends of chromosomes (telomeres) in vivo. The interaction between topoisomerase II and telomeres represents a model system to explore the enzyme's recognition of biologically important DNA repeat elements that are widespread in the human genome. A comprehensive study of the endogenous interplay between eukaryotic topoisomerase II and telomeres is proposed to craft the convergence of these two areas to create new inroads for chemotherapeutic intervention in cancer and to integrate, these concepts with events related to cellular senescence and aging.